The pulmonary lipofibroblast is located in the alveolar interstitium where it is distinguished by the presence of large, cytoplasrnic lipid droplets (Heid et al. (1996) Biochem J., 320 (Pt 3):1025-1030; Torday et al. (1995) Biochim Biophys Acta., 1254(2): 198-206). These cells were first described by O'Hare and Sheridan in 1970 (Nicholas et al. J Appl Physiol. 53(6): 1521-1528), and their biochemical and structural characteristics were determined during the late 1970s and early 1980s by Brody's group (Heid et al. (1996) Biochem J., 320 (Pt 3):1025-1030; Maksvytis et al. (1984) J Cell Physiol., 118(2):113-123; Maksvytis et al. (1981) Lab Invest. 45(3): 248-259; Torday et al. (1995) Biochim Biophys Acta., 1254(2): 198-206), which named them lipid interstitial cells. McGowan and Torday (McGowan and Torday (1997) Annu Rev Physiol. 59: 43-62) have recently critically reviewed the literature on the contributions of these cells to alveolar development and have termed them lipofibroblasts to highlight their fibroblast-like phenotype.
Torday and colleagues (Miura et al. (2002) J Biol Chem. 277(35): 32253-32257; Nunez and Torday (1995) J Nutr. 125(6 Suppl): 1639S-1644S) have investigated the prenatal ontogeny of the fetal rat lung lipofibroblast, showing a four- to fivefold increase of triacylglycerol in isolated lipofibroblasts, paralleling that in whole lung (Shannon et al. (2001) Am J Respir Cell Mol Biol. 24(3):235-244), over the last 4 days of gestation. The triacylglycerol content of fetal rat lung lipofibroblasts is maximal just before the appearance of surfactant phospholipid-containing lamellar bodies in neighboring alveolar type II epithelial (EPII) cells, the site of pulmonary surfactant synthesis (Rodriguez et al. (2001) Exp Lung Res. 27(1): 13-24). Torday and coworkers have demonstrated in a coculture system that the triacylglycerols of fibroblast origin are used for surfactant phospholipid synthesis by EPII cells (Rubin et al. (2004) Dev Dyn. 230(2): 278-289; Torday et al (1995) BBA 1254(2): 198-206) and that the metabolism of these lipids in the culture system is regulated by hormones important for lung maturation (Miura et al. (2002) J Biol Chem. 277(35): 32253-32257; Nunez and Torday (1995) J Nutr. 125(6 Suppl): 1639S-1644S).
In most mammalian cells, neutral lipids, including those found in pulmonary lipofibroblasts (LIFs), are stored in discrete lipid storage droplets, which are composed of a core of triacylglycerol and cholesterol esters surrounded by a limiting osmophilic boundary (Brasaemle et al. (1997) J Lipid Res. 38(11): 2249-2263). Little is known about the proteins that are present at the surface of these lipid storage droplets. The first-described intrinsic lipid droplet-associated proteins were the perilipins, which localize to the periphery of the intracellular neutral lipid storage droplets in adipocytes (Adamson et al. (1991) Exp Lung Res. 17(4): 821-835; Gao and Serrero (1999) J Biol Chem. 274(24): 16825-16830; Laemmli (1970) Nature 227(259): 680-685; O'Hare and Sheridan (1970) Am J Anat. 127(2): 181-205) and steroidogenic cells of the adrenal cortex, testes, and ovaries (O'Hare and Sheridan (1970) Am J Anat. 127(2): 181-205). Perilipins share sequence homology with adipocyte differentiation-related protein (ADrP), which was first identified as a gene expressed very early in adipocyte differentiation (Heid et al. (1998) Cell Tissue Res., 294(2): 309-321). ADrP, transfected into COS cells, has been shown to play a role in facilitated fatty acid uptake (Frolov et al. (2000) J Biol Chem. 275(17): 12769-12780). ADrP mRNA has subsequently been found to be expressed in a wide variety of somatic tissues: heart, brain, spleen, liver, skeletal muscle, kidney, testes, and most pronouncedly in the lung (Brasaemle et al. (1997) J Lipid Res. 38(11): 2249-2263; Laemmli (1970) Nature 227(259): 680-685). The expression level of ADrP mRNA in adult mouse lung was found to be second only to that in adipose tissue, the tissue that stores the greatest amount of neutral lipid and has the highest expression of ADrP mRNA (Brasaemle et al. (1997) J Lipid Res. 38(11): 2249-2263). Schultz et al have determined that lipofibroblasts express ADRP, but that neighboring alveolar type II cells express little if any ADRP. Furthermore, ADRP binds to type II cells, facilitating uptake and incorporation of triglyceride into surfactant phospholipid. ADrP was also identified in human tissues and named adipophilin (Greenberg et al. (1993) Proc Natl Acad Sci USA., 90(24): 12035-12039).